This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary goal of the project is to obtain intermediate resolution structures of the open and closed conformations of the KATP channel. The KATP channel is a metabolic sensor that couples changes in glucose metabolism to membrane electrical activity. In the pancreatic beta cell, KATP dependent membrane depolarization leads to downstream insulin release. Mutations in the channel have been implicated in a wide range of metabolic disorders including neonatal diabetes, type 2 diabetes, and persistent hyperinsulinemia hypoglycemia of infancy.